RESEARCH AND DEVELOPMENT | PIPELINE

ARV-102 is an investigational, orally bioavailable and brain-penetrant PROTAC designed to specifically target and degrade leucine-rich repeat kinase (LRRK2) for the potential treatment of neurodegenerative diseases, including Parkinson’s disease and progressive supranuclear palsy (PSP). Preclinical and clinical data support LRRK2 as a therapeutic target for these indications.

Parkinson’s disease is a progressive brain disorder that damages dopamine-producing neurons, leading to progression of symptoms including motor-related symptoms like tremors and limb stiffness, as well as non-motor symptoms including depression, sleep disorders, cognitive decline, and more. LRRK2 activity is abnormally increased in Parkinson’s—and experimental studies strongly suggest that blocking LRRK2 may be neuroprotective.

PSP is a rare, rapidly progressing neurodegenerative disorder that affects brain cells that control balance and coordination, eye movement, speech, swallowing, and thinking. Symptoms may start as early as in a patient’s 40’s, and is characterized by widespread tau pathology. LRRK2 influences tau pathology by directly modifying it and indirectly by disrupting cellular processes (actin, mitochondria, endocytosis) crucial for tau’s normal function and clearance, promoting its toxic accumulation and spread.

ARV-027 is an investigational oral, peripherally restricted PROTAC degrader designed to selectively target and eliminate toxic polyglutamine-expanded androgen receptor (polyQ-AR) in skeletal muscle to potentially treat spinal-bulbar muscular atrophy (SBMA).

SBMA (also known as Kennedy’s disease) is a rare, X-linked, genetically defined neuromuscular disease caused by a CAG trinucleotide repeat expansion (polyQ) in the androgen receptor (AR) gene, causing protein misfolding and leading to progressive degeneration of the neuromuscular system in men. The disease usually begins between the ages of 30 and 50 and there are currently no approved disease-modifying therapies. In preclinical mouse models, ARV-027 induced polyQ-AR degradation in muscle tissues and rescued both strength and endurance.

ARV-393 is an investigational, orally bioavailable PROTAC designed to specifically target and degrade B-cell lymphoma 6 protein (BCL6), a transcriptional repressor and major driver of B-cell lymphomas. Also as a lineage defining transcription factor of T-follicular helper cells, BCL6 has been implicated in nodal T-follicular helper cell lymphoma (nTFHL), including the angioimmunoblastic type, formerly angioimmunoblastic T-cell lymphoma (AITL).

Despite significant progress made with treating B-cell non-Hodgkin lymphoma (NHL) and nTFHL, many patients will ultimately experience disease progression or relapse. Thus, there remains an unmet need for novel mechanisms (like BCL6 degradation) and drug combinations that may be able to improve clinical outcomes.

ARV-806 is an investigational novel PROTAC designed to selectively target and degrade mutant Kirsten rat sarcoma (KRAS) G12D in solid tumors.

The KRAS protein is a key regulator of cell growth and survival and normally functions by cycling between an active “ON” and inactive “OFF” state. Mutations lead to constitutive activation of these signaling pathways, leading to cancer. KRAS G12D is the most common KRAS mutant found in solid tumors, with preclinical and clinical data supporting its value as a therapeutic target. There are currently no approved therapies that specifically target KRAS G12D mutations. ARV-806 has the potential to address high unmet need in solid tumors, such as pancreatic, colorectal, and non-small cell lung cancer (NSCLC).

ARV-6723 is an investigational oral PROTAC designed to degrade hematopoietic progenitor kinase 1 (HPK1) in solid malignancies and is Arvinas’ first clinical candidate in the immuno-oncology (IO) space.

In solid tumor malignancies, such as non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC), HPK1 acts as a negative regulator of T-cell receptor signaling, contributing to T-cell exhaustion and suppressing antitumor immunity. Further, HPK1 has a regulatory role in other immune cell types (NK, DC, B cells, etc.) that can be co-opted by tumors, thus enabling these cancers to resist IO therapy. New therapies are needed to address the immunosuppressive activities of HPK1 driven by a dysfunctional tumor microenvironment.

Vepdegestrant is an investigational, orally bioavailable PROTAC estrogen receptor (ER) degrader being developed for the treatment of ER positive / human epidermal growth factor receptor 2 (HER2) negative (ER+/HER2-) locally advanced or metastatic breast cancer. In the VERITAC-2 Phase 3 clinical trial, vepdegestrant demonstrated statistically significant and clinically meaningful improvement in progression free survival compared to fulvestrant in patients with ER+/HER2- ESR1-mutated advanced or metastatic breast cancer previously treated with endocrine-based therapy.

Breast cancer is the most common cancer among women in the U.S. and worldwide. Many breast cancers are known to be driven by estrogen receptor signaling. While women with metastatic ER+/HER2- breast cancer are often treated with hormone therapy (also referred to as endocrine therapy), patients with aggressive disease or whose disease continues to progress with a hormonal treatment regimen may benefit from additional therapies targeting the estrogen receptor. It is estimated that for those previously treated with endocrine therapy and a CDK4/6 inhibitor for metastatic disease, ESR1m mutations occur in up to 40%-50% of patients.

In September 2025, Arvinas and Pfizer announced their plan to jointly select a third party for the commercialization and potential further development of vepdegestrant.

Luxdegalutamide is an investigational, orally bioavailable PROTAC androgen receptor (AR) degrader. In April 2024, Arvinas entered into a global license agreement with Novartis for the development and commercialization of luxdegalutamide for the treatment of prostate cancer, and Novartis is progressing luxdegalutamide in multiple clinical studies. Learn more.